Mesothelin mediates platinum resistance in high-grade serous ovarian cancer and serves as a predictive marker for chemotherapy sensitivity
10.3969/j.issn.1672-8467.2024.06.001
- VernacularTitle:间皮素介导高级别浆液性卵巢癌铂化疗耐药并作为化疗敏感性的预测指标
- Author:
Yu-Jing ZHONG
1
;
Yi-Ying WANG
;
Hai-Ou LIU
;
Jia-Qi LU
Author Information
1. 复旦大学附属妇产科医院妇科 上海 200090
- Keywords:
mesothelin(MSLN);
high-grade serous ovarian carcinoma(HGSOC);
cisplatin;
chemotherapy resistance
- From:
Fudan University Journal of Medical Sciences
2024;51(6):873-881
- CountryChina
- Language:Chinese
-
Abstract:
Objective To elucidate the potential mechanisms by which mesothelin(MSLN)contributes to chemotherapy resistance in high-grade serous ovarian cancer(HGSOC).Methods A Meta-analysis utilizing public ovarian cancer databases was performed to evaluate the correlation between MSLN expression levels and overall survival(OS)in ovarian cancer patients.Pathway enrichment analysis was employed to identify key signaling pathways regulated by MSLN and their roles in chemotherapy resistance.Additionally,the TCGA-HGSOC database was analyzed to examine genomic features associated with MSLN-mediated chemotherapy resistance.To validate the biological function of MSLN in chemotherapy resistance,an intraperitoneal metastasis model was established using MSLN-knockdown ID8 ovarian cancer cells in mice.Results Elevated MSLN expression was significantly associated with poor patient prognosis(HR:1.42,95%CI:1.16-1.74).Differential gene expression and pathway enrichment analyses revealed that high MSLN expression upregulates resistance-associated genes and pathways involved in drug metabolism and DNA-binding signaling.Genomic association analysis showed a negative correlation between high MSLN expression and chromosomal instability features,specifically CX3,CX11,and CX13 scores.In vivo studies demonstrated that MSLN knockdown enhanced the tumor-suppressive effects of cisplatin.Conclusion High MSLN expression represents a potential biomarker for poor prognosis and chemotherapy resistance in HGSOC patients,suggesting MSLN as a promising target for therapeutic intervention.
